CD73 Is Associated with Poor Prognosis in High-Grade Serous Ovarian Cancer

被引：202

作者：

Turcotte, Martin ^{[1
,2
,3
]}

Spring, Kathleen ^{[1
,2
]}

Pommey, Sandra ^{[1
,2
]}

Chouinard, Guillaume ^{[1
,2
]}

Cousineau, Isabelle ^{[1
,2
]}

George, Joshy ^{[4
]}

Chen, Gregory M. ^{[5
,6
]}

Gendoo, Deena M. A. ^{[5
,6
]}

Haibe-Kains, Benjamin ^{[5
,6
]}

Karn, Thomas ^{[7
]}

Rahimi, Kurosh ^{[1
,8
,9
]}

Le Page, Cecile ^{[1
,2
]}

Provencher, Diane ^{[1
,2
,9
,10
]}

Mes-Masson, Anne-Marie ^{[1
,2
,9
,10
]}

Stagg, John ^{[1
,2
,3
]}

机构：

[1] Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ H2X 0A9, Canada

[2] Univ Montreal, Inst Canc Montreal, Montreal, PQ H2L 4M1, Canada

[3] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada

[4] Jackson Lab Genom Med, Computat Sci & Stat Anal, Farmington, CT USA

[5] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[6] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[7] Univ Hosp Frankfurt, Dept Obstet & Gynecol, Frankfurt, Germany

[8] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada

[9] Ctr Hosp Univ Montreal, Dept Pathol, Montreal, PQ H2X 0A9, Canada

[10] Univ Montreal, Dept Obstet & Gynecol, Div Gynecol Oncol, Montreal, PQ, Canada

来源：

CANCER RESEARCH | 2015年 / 75卷 / 21期

关键词：

NEGATIVE BREAST-CANCER; T-CELLS; TARGETING CD73; TUMOR-GROWTH; CARCINOMA; EXPRESSION; ADENOSINE; SURVIVAL; STAGE; DIFFERENTIATION;

D O I：

10.1158/0008-5472.CAN-14-3569

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The cell surface nucleotidase CD73 is an immunosuppressive enzyme involved in tumor progression and metastasis. Although preclinical studies suggest that CD73 can be targeted for cancer treatment, the clinical impact of CD73 in ovarian cancer remains unclear. In this study, we investigated the prognostic value of CD73 in high-grade serous (HGS) ovarian cancer using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with shorter disease-free survival and overall survival in patients with HGS ovarian cancer. Furthermore, high levels of CD73 expression in ovarian tumor cells abolished the good prognosis associated with intraepithelial CD8(+) cells. Notably, CD73 gene expression was highest in the C1/stromal molecular subtype of HGS ovarian cancer and positively correlated with an epithelial-to-mesenchymal transition gene signature. Moreover, in vitro studies revealed that CD73 and extracellular adenosine enhance ovarian tumor cell growth as well as expression of antiapoptotic BCL-2 family members. Finally, in vivo coinjection of ID8 mouse ovarian tumor cells with mouse embryonic fibroblasts showed that CD73 expression in fibroblasts promotes tumor immune escape and thereby tumor growth. In conclusion, our study highlights a role for CD73 as a prognostic marker of patient survival and also as a candidate therapeutic target in HGS ovarian cancers. (C) 2015 AACR.

引用

页码：4494 / 4503

页数：10

共 40 条

[1] PD-L1 on Tumor Cells Is Induced in Ascites and Promotes Peritoneal Dissemination of Ovarian Cancer through CTL Dysfunction [J].